High-Dose Cytarabine-Based Consolidation Shows Superior Results for Elderly AML Patients with Intermediate Risk Cytogenetics in First Complete Remission

In elderly patients with acute myeloid leukemia (AML) treated intensively, the optimal post-remission strategy is unclear. High dose cytarabine (HiDAC) 3 g/m² is the standard consolidation dose for younger adults with AML with favorable and intermediate risk disease, but is associated with high rates of severe toxicity and early death in older adults that counteract any improvement in efficacy when compared to standard dose cytarabine. We have used a modified high-dose cytarabine consolidation regimen, and compared this to a similar cohort receiving a conventional-dose regimen.

164 patients with AML age 60 years and over, who achieved complete remission after standard induction therapy consisting of cytarabine 100 mg/m²/day continuous IV infusion × 7 days and dauorubicin 60 mg/m² IV daily × 3 (7+3) from 1998 – 2008, received two different types of post-remission therapy in sequential cohorts. Group 1 (n=55), treated from 1998–2002, received 2 consolidation cycles, each consisting of cytarabine 1.5 g/m² q12h × 6 doses + daunorubicin 45 mg/m2/day × 2, while group 2 (n=109), treated from 2003–2008, received a first consolidation using 7+3 followed by a second cycle consisting of mitoxantrone 10 mg/m² IV daily × 5 plus etoposide 100 mg/m² IV daily × 5 (NOVE).

The two groups did not differ with respect to median age (68 vs. 69 years), mean baseline WBC, gender, prior malignancy/AHD and proportion of patients undergoing allogeneic HSCT in CR-1 (9.1 vs.8.3%). 40 patients (72.7%) in the first group, and 86 patients (78.9%) in the second group received the intended consolidation regimen (p=0.38). Among the entire cohort (n=164), and in the subgroup with adverse risk cytogenetics, there was no significant difference in OS or DFS between the two groups. For patients with intermediate risk cytogenetics, on an intention-to-treat basis, the disease-free survival (DFS) was significantly higher for group 1 vs. group 2 (Table 1).

Older patients with intermediate-risk cytogenetics, who received a modified high-dose cytarabine-based consolidation regimen combined with anthracycline, had a superior DFS and a trend toward superior OS, as compared to those who received conventional-dose consolidation therapy. These findings require further evaluation in a prospective randomized study but, if confirmed, suggest that older fit patients with intermediate risk cytogenetics should receive more intensified post-remission therapy with modified high-dose cytarabine.

No relevant conflicts of interest to declare.